The molecular basis for the sexual differentiation of neural structure and function is being investigated in three organisms. In humans, the possible role of heredity in sexual orientation is probed by pedigree analysis, candidate gene screening, and molecular linkage studies. A correlation between male sexual orientation and the inheritance of DNA markers on chromosomal region Xq28 has been detected within a subpopulation of families in which there are two homosexual brothers. This candidate locus is distinct from the androgen receptor locus at Xq13. In Drosophila, attempts to clone the fruitless locus, which leads to male- male courtship behavior, have been initiated. In rat, mRNA has been prepared from a sexually dimorphic region of the hypothalamus and is being screened for sex-specific and androgen-dependent differences.